A Cure for Cancer? The Therapeutic Potential of Combining Oncolytic Viruses and Chimeric Antigenic Receptor T-Cell Therapy

SUMMARY Cancer continues to be a devastating diagnosis. Fortunately, active research has developed and refined two cancer therapies: oncolytic virotherapy and the novel chimeric antigen receptor (CAR) T-cell therapy. The former utilizes oncolytic viruses (OVs) that preferentially infect and kill cancer cells over healthy, non-cancerous tissues. The latter isolates the patient’s T-cells, uses a disarmed virus to insert genes expressing genetically engineered receptors, known as chimeric antigen receptors, which target tumor-associated antigens on malignant cells. Despite several clinical successes with both herapies, limitations exist which prevent their medicinal potentials from being achieved. Oncolytic viruses are often completely sequestered or neutralized due to human physiology and pre-existing adaptive immunity. CAR T-cells seldom enter solid tumors due to an insufficient number of chemokines secreted by the tumor, or because tumor-associated antigens are rarely released. Even if entry occurs, the tumor microenvironment is often in an immunosuppressed state that greatly diminishes T-cells from functioning. Remarkably, it has been previously reported that the administration of oncolytic viruses into patients, even with sequestration, can result in the release of neoantigens from tumors, which may promote entry of CAR T-cells into solid tumors. Furthermore, oncolytic viruses have been shown to reverse the immunosuppressive environment of certain tumors. With this, CAR T-cells may be able to perform their critical role of orchestrating the immune system to kill malignancies. For the millions of individuals who will be diagnosed with cancer, it is critical that researchers investigate the therapeutic potential of combining oncolytic virotherapy and chimeric antigen receptor T-cell therapy.